RARE DISEASE
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis
Synonyms: Extrinsic allergic alveolitis
Synonyms: Extrinsic allergic alveolitis
Synonyms: Extrinsic allergic alveolitis
Drug discovery
0
drugs
With orphan designations
Overview
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by inhaled antigens (e.g., mold, bird proteins, organic/chemical particles), causing alveoli inflammation and granuloma formation. It presents as acute (flu-like symptoms resolving with exposure cessation) or chronic (progressive dyspnea, cough, fibrosis). Diagnosis relies on clinical history, HRCT patterns (ground-glass opacities, mosaicism), bronchoalveolar lavage lymphocytosis, and biopsy if uncertain [1][6][11]. Early antigen avoidance prevents progression, while chronic fibrosis carries poor prognosis [1][3][9].
Burden
Chronic fibrotic HP has a 5-year mortality rate of ~60% without transplant [1][11].
Accounts for 1.28–2.71 cases per 100,000 annually, with up to 25% progressing to fibrosis [2][4][7].
Leads to substantial disability, frequent hospitalizations, and high healthcare costs due to oxygen dependence/pulmonary rehab [9][11][16].
Therapies
Primary: Strict antigen avoidance; environmental modifications (humidity control, ventilation) [3][8][15].
Pharmacologic: Corticosteroids (prednisone) for acute/subacute cases; antifibrotics (nintedanib) or immunosuppressants (azathioprine) for progressive fibrotic HP [3][9][13].
Advanced: Lung transplantation for end-stage fibrosis [3][15].
Categories: rare allergic disease, rare respiratory diseases, rare transplant-related disorders
Research Papers
598 drug discovery papers about Hypersensitivity pneumonitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
598 drug discovery papers about Hypersensitivity pneumonitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-05 | Does bronchoalveolar lavage lymphocytosis predict prognosis in fibrotic hypersensitivity pneumonitis, and is this relationship influenced by low-dose immunomodulatory therapy at the time of BAL?
Bronchoalveolar lavage (BAL) lymphocytosis is associated with improved prognosis in fibrotic hypersensitivity pneumonitis (fHP), although its prognostic value is unclear in patients receiving immunomodulatory treatment. We investigated whether treatment tapered to the lowest tolerated level at the time of BAL modifies associations with disease severity, one-year lung function, and transplant-free survival. We analysed 247 fHP patients undergoing BAL, including 162 untreated and 85 receiving immunomodulatory therapy at the time of BAL. Associations between BAL lymphocytosis and baseline composite physiologic index (CPI), one-year CPI change, and transplant-free survival were assessed using multivariable flexible parametric survival models incorporating treatment status and interaction terms, adjusted for covariates. Mean age was 63 years, 43% male, 37% ever-smokers. Treated patients at the time of BAL were younger, with more severe disease (higher CPI). Mean BAL lymphocyte percentages were similar between two groups and inversely associated with baseline CPI in both. Higher BAL lymphocyte% were associated with more favourable CPI change in both untreated (-1.7 points per 10% increase; 95%CI -2.5--0.8, p < 0.0001) and treated patients at BAL (-2.0 points; 95% CI -3.1--0.9, p < 0.0001), with no treatment-by-BAL lymphocyte interaction (p = 0.64). Higher BAL lymphocyte% independently predicted lower mortality both in untreated (HR 0.87 per 10% increase, p = 0.036) and treated patients at the time of BAL (HR 0.78, p = 0.025), with no treatment-by-BAL lymphocyte interaction (p = 0.39). BAL lymphocytosis was associated with less severe disease, favourable one-year CPI change and better survival, irrespective of background immunomodulatory therapy.
2026-07-16 | Laboratory and field performance of 2-(thiocyanomethylthio)benzothiazole against fast-growing nontuberculous mycobacteria found in metalworking fluid.
Uncontrolled, fast-growing nontuberculous mycobacteria (NTM) in metalworking fluids (MWFs) can cause dermal lesions, hypersensitivity pneumonitis, and other health complications in exposed metalworkers. Although biocides are routinely used to control microbial growth in MWF, they are often ineffective because they are unsuitable for the physical or chemical conditions of the system, added infrequently, or ineffective against the microorganisms present. Given the increasing concern for NTM in industrial settings, there is a growing need for MWF-compatible (i.e., nonoxidizing) biocides that are effective against NTM. Here, we evaluated the efficacy of four nonoxidizing biocides against fast-growing NTM species in water-based MWF. Results from a 72-hr laboratory challenge indicated that biocides containing 2-(thiocyanomethylthio)benzothiazole (TCMTB), commonly used as a fungicide, were most effective at controlling Mycobacterium chelonae, M. fortuitum, and field and laboratory strains of M. immunogenum. In subsequent field trials at nine MWF plants where workers had reported symptoms of dermal and lung illnesses, TCMTB consistently reduced viable NTM counts, as measured through both culture-based assays and microscopy. However, dosages needed to be increased two- to four-fold relative to the laboratory experiments to control NTM populations in systems with established biofilms. Due to the observed success of TCMTB against NTM in field context, the manufacturing plants involved in this study continued regular application of TCMTB as a preventative treatment. No additional outbreaks were observed throughout our follow-up period, which, in several cases, spanned approximately 10 years. The results suggest that TCMTB may provide an efficacious method for treating and preventing NTM contamination in MWF systems. Future studies should explore the mechanism of action of the sulfur-rich chemical structure of TCMTB to potentially guide the development and synthesis of related compounds with anti-NTM properties. One sentence summary 2--(thiocyanomethylthio)benzothiazole kills fast-growing nontuberculous mycobacteria, including Mycobacterium immunogenum, and prevents worker infections based on laboratory, field trial, and long-term (6-10 years) industrial studies.
2026-07-11 | Mycophenolate and Azathioprine in Fibrotic Interstitial Lung Disease.
Immunosuppression is routinely used for non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), despite limited trial evidence and unclear impact on long-term outcomes. To evaluate whether mycophenolate or azathioprine improves three-year transplant-free survival and lung function trajectory in fibrotic ILD, including non-IPF idiopathic interstitial pneumonia (IIP), fibrotic hypersensitivity pneumonitis (fHP), and connective-tissue disease (CTD) associated ILD. We employed a clone-censor-weighting framework to emulate a randomized controlled trial in this multi-center retrospective study. Each patient was cloned and assigned to immunosuppression initiation within 6 months of enrollment or no initiation strategies, and censored when the assigned strategy deviated from observed treatment. Stabilized inverse probability treatment and censoring weights were used. The primary endpoint was three-year transplant-free survival assessed with weighted Cox models across treatment strategies. Weighted generalized estimating equations were used to model lung function trajectory. Among 2,270 included patients, 18% (186/1022) with non-IPF IIP, 30% (162/544) with fHP, and 31% (221/704) with CTD-ILD were initiated on immunosuppression within 6-months. Immunosuppression was not associated with improved survival within any ILD subtype but was associated with worse survival in non-IPF IIP (HR 1.38, 95% CI 1.04-1.84) and fHP (HR 1.62, 95% CI 1.09-2.40). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype. In this study, immunosuppression initiation showed no evidence of benefit for three-year transplant-free survival or lung function and was associated with higher mortality in select fibrotic ILD subtypes. Prospective randomized controlled trials are needed to inform patient care.
2026-07-10 | Smartwatch-Derived SpO2 Trends During Disease Worsening and Treatment Response in Fibrotic Hypersensitivity Pneumonitis: A Case Report.
Consumer smartwatches can provide longitudinal peripheral oxygen saturation (SpO2) estimates for wellness purposes, but there is limited evidence that they can be used to monitor respiratory disease. In this study, we described a 52-year-old man with fibrotic hypersensitivity pneumonitis who developed exertional hypoxemia, which progressed radiologically and led to functional decline. Systemic corticosteroids improved his symptoms, imaging, and lung function. The monthly mean Apple Watch SpO2 dropped from 95.7% to 94.4% within 3 months of the worsening and recovered to 96.5% 4 weeks after corticosteroid initiation. Daily-life SpO2 trends from smartwatches may be useful for monitoring respiratory diseases.
2026-06-30 | [Dyspnea, pulmonary mosaic sign and pulmonary hypertension].
This case report presents a young female patient whose chief complaint was exertional dyspnea. Right heart catheterization confirmed severe pulmonary hypertension. Concurrently, chest CT showed atypical pulmonary parenchymal and interstitial lesions, and pulmonary function tests indicated severe impairment of diffusion capacity. To clarify whether an association existed between the lung disease and pulmonary hypertension, transbronchial lung cryobiopsy was performed, which revealed multinucleated giant cell aggregates within the alveolar spaces, with cholesterol clefts in the cytoplasm of some of them. Together with a 1-year history of pigeon exposure, the final pulmonary diagnosis was extrinsic allergic alveolitis (hypersensitivity pneumonitis).With respect to the pulmonary hypertension, genetic testing showed no significant abnormalities, thereby ruling out heritable pulmonary hypertension. After oral imatinib combined with macitentan was administered, the patient's pulmonary artery pressure gradually decreased and her symptoms recovered well; however, follow-up chest CT and pulmonary function tests showed no apparent improvement. Because the elevated pulmonary artery pressure was inconsistent with the pulmonary disease, the patient was ultimately diagnosed with idiopathic pulmonary hypertension complicated by allergic alveolitis.
2026-08-05 | Does bronchoalveolar lavage lymphocytosis predict prognosis in fibrotic hypersensitivity pneumonitis, and is this relationship influenced by low-dose immunomodulatory therapy at the time of BAL?
Bronchoalveolar lavage (BAL) lymphocytosis is associated with improved prognosis in fibrotic hypersensitivity pneumonitis (fHP), although its prognostic value is unclear in patients receiving immunomodulatory treatment. We investigated whether treatment tapered to the lowest tolerated level at the time of BAL modifies associations with disease severity, one-year lung function, and transplant-free survival. We analysed 247 fHP patients undergoing BAL, including 162 untreated and 85 receiving immunomodulatory therapy at the time of BAL. Associations between BAL lymphocytosis and baseline composite physiologic index (CPI), one-year CPI change, and transplant-free survival were assessed using multivariable flexible parametric survival models incorporating treatment status and interaction terms, adjusted for covariates. Mean age was 63 years, 43% male, 37% ever-smokers. Treated patients at the time of BAL were younger, with more severe disease (higher CPI). Mean BAL lymphocyte percentages were similar between two groups and inversely associated with baseline CPI in both. Higher BAL lymphocyte% were associated with more favourable CPI change in both untreated (-1.7 points per 10% increase; 95%CI -2.5--0.8, p < 0.0001) and treated patients at BAL (-2.0 points; 95% CI -3.1--0.9, p < 0.0001), with no treatment-by-BAL lymphocyte interaction (p = 0.64). Higher BAL lymphocyte% independently predicted lower mortality both in untreated (HR 0.87 per 10% increase, p = 0.036) and treated patients at the time of BAL (HR 0.78, p = 0.025), with no treatment-by-BAL lymphocyte interaction (p = 0.39). BAL lymphocytosis was associated with less severe disease, favourable one-year CPI change and better survival, irrespective of background immunomodulatory therapy.
2026-07-16 | Laboratory and field performance of 2-(thiocyanomethylthio)benzothiazole against fast-growing nontuberculous mycobacteria found in metalworking fluid.
Uncontrolled, fast-growing nontuberculous mycobacteria (NTM) in metalworking fluids (MWFs) can cause dermal lesions, hypersensitivity pneumonitis, and other health complications in exposed metalworkers. Although biocides are routinely used to control microbial growth in MWF, they are often ineffective because they are unsuitable for the physical or chemical conditions of the system, added infrequently, or ineffective against the microorganisms present. Given the increasing concern for NTM in industrial settings, there is a growing need for MWF-compatible (i.e., nonoxidizing) biocides that are effective against NTM. Here, we evaluated the efficacy of four nonoxidizing biocides against fast-growing NTM species in water-based MWF. Results from a 72-hr laboratory challenge indicated that biocides containing 2-(thiocyanomethylthio)benzothiazole (TCMTB), commonly used as a fungicide, were most effective at controlling Mycobacterium chelonae, M. fortuitum, and field and laboratory strains of M. immunogenum. In subsequent field trials at nine MWF plants where workers had reported symptoms of dermal and lung illnesses, TCMTB consistently reduced viable NTM counts, as measured through both culture-based assays and microscopy. However, dosages needed to be increased two- to four-fold relative to the laboratory experiments to control NTM populations in systems with established biofilms. Due to the observed success of TCMTB against NTM in field context, the manufacturing plants involved in this study continued regular application of TCMTB as a preventative treatment. No additional outbreaks were observed throughout our follow-up period, which, in several cases, spanned approximately 10 years. The results suggest that TCMTB may provide an efficacious method for treating and preventing NTM contamination in MWF systems. Future studies should explore the mechanism of action of the sulfur-rich chemical structure of TCMTB to potentially guide the development and synthesis of related compounds with anti-NTM properties. One sentence summary 2--(thiocyanomethylthio)benzothiazole kills fast-growing nontuberculous mycobacteria, including Mycobacterium immunogenum, and prevents worker infections based on laboratory, field trial, and long-term (6-10 years) industrial studies.
2026-07-11 | Mycophenolate and Azathioprine in Fibrotic Interstitial Lung Disease.
Immunosuppression is routinely used for non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), despite limited trial evidence and unclear impact on long-term outcomes. To evaluate whether mycophenolate or azathioprine improves three-year transplant-free survival and lung function trajectory in fibrotic ILD, including non-IPF idiopathic interstitial pneumonia (IIP), fibrotic hypersensitivity pneumonitis (fHP), and connective-tissue disease (CTD) associated ILD. We employed a clone-censor-weighting framework to emulate a randomized controlled trial in this multi-center retrospective study. Each patient was cloned and assigned to immunosuppression initiation within 6 months of enrollment or no initiation strategies, and censored when the assigned strategy deviated from observed treatment. Stabilized inverse probability treatment and censoring weights were used. The primary endpoint was three-year transplant-free survival assessed with weighted Cox models across treatment strategies. Weighted generalized estimating equations were used to model lung function trajectory. Among 2,270 included patients, 18% (186/1022) with non-IPF IIP, 30% (162/544) with fHP, and 31% (221/704) with CTD-ILD were initiated on immunosuppression within 6-months. Immunosuppression was not associated with improved survival within any ILD subtype but was associated with worse survival in non-IPF IIP (HR 1.38, 95% CI 1.04-1.84) and fHP (HR 1.62, 95% CI 1.09-2.40). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype. In this study, immunosuppression initiation showed no evidence of benefit for three-year transplant-free survival or lung function and was associated with higher mortality in select fibrotic ILD subtypes. Prospective randomized controlled trials are needed to inform patient care.
2026-07-10 | Smartwatch-Derived SpO2 Trends During Disease Worsening and Treatment Response in Fibrotic Hypersensitivity Pneumonitis: A Case Report.
Consumer smartwatches can provide longitudinal peripheral oxygen saturation (SpO2) estimates for wellness purposes, but there is limited evidence that they can be used to monitor respiratory disease. In this study, we described a 52-year-old man with fibrotic hypersensitivity pneumonitis who developed exertional hypoxemia, which progressed radiologically and led to functional decline. Systemic corticosteroids improved his symptoms, imaging, and lung function. The monthly mean Apple Watch SpO2 dropped from 95.7% to 94.4% within 3 months of the worsening and recovered to 96.5% 4 weeks after corticosteroid initiation. Daily-life SpO2 trends from smartwatches may be useful for monitoring respiratory diseases.
2026-06-30 | [Dyspnea, pulmonary mosaic sign and pulmonary hypertension].
This case report presents a young female patient whose chief complaint was exertional dyspnea. Right heart catheterization confirmed severe pulmonary hypertension. Concurrently, chest CT showed atypical pulmonary parenchymal and interstitial lesions, and pulmonary function tests indicated severe impairment of diffusion capacity. To clarify whether an association existed between the lung disease and pulmonary hypertension, transbronchial lung cryobiopsy was performed, which revealed multinucleated giant cell aggregates within the alveolar spaces, with cholesterol clefts in the cytoplasm of some of them. Together with a 1-year history of pigeon exposure, the final pulmonary diagnosis was extrinsic allergic alveolitis (hypersensitivity pneumonitis).With respect to the pulmonary hypertension, genetic testing showed no significant abnormalities, thereby ruling out heritable pulmonary hypertension. After oral imatinib combined with macitentan was administered, the patient's pulmonary artery pressure gradually decreased and her symptoms recovered well; however, follow-up chest CT and pulmonary function tests showed no apparent improvement. Because the elevated pulmonary artery pressure was inconsistent with the pulmonary disease, the patient was ultimately diagnosed with idiopathic pulmonary hypertension complicated by allergic alveolitis.
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